Clindamycin

Indications

Clindamycin is FDA-approved for the treatment of septicemia, intra-abdominal infections, lower respiratory infections, gynecological infections, bone and joint infections, and skin and skin structure infections. Clindamycin is also used in the treatment of streptococcal pharyngitis, acne vulgaris, bacterial vaginosis and severe pelvic inflammatory disease. Although not a first-line treatment, Infectious Diseases Society of America (IDSA) has published guidelines for using intravenous (IV) clindamycin for the inpatient treatment of community-acquired pneumonia. Dentists will use clindamycin for prophylactic coverage against endocarditis. Anesthesiologists and surgeons will often administer clindamycin per American Society of Health-System Pharmacists (ASHP) and IDSA guidelines as prophylaxis in the operating room.

Additionally, clindamycin can be used to treat babesiosis, anthrax, and malaria. Clindamycin is also commonly used in skin and soft tissue infections that are uncomplicated. Clindamycin is used in soft tissue infections when due to its efficacy against MRSA. Clindamycin is also chosen for outpatient treatment because of its cost, availability, and effectiveness against methicillin-resistant Staphylococcus aureus.

Mechanism of Action

Clindamycin prevents peptide bond formation, thereby inhibiting protein synthesis, by reversibly binding to 50S ribosomal subunits. Depending on the organism, infection site, and drug concentration, clindamycin may be a bacteriostatic or bactericidal antibiotic. When taken orally, absorption cannot take place until clindamycin palmitate is hydrolyzed in the gastrointestinal (GI) tract. It is then distributed to across the body in tissue and other regions containing blood. Clindamycin cannot efficiently penetrate meninges very well and is therefore not an antibiotic of choice for infections of the cerebrospinal fluid (CSF). As it travels through the bloodstream, clindamycin is primarily bound to protein. Clindamycin is primarily metabolized in the liver by CYP 3A4 (major) and CYP 3A5 which oxidize the antibiotic into clindamycin sulfoxide (primary metabolite) and N-desmethyl clindamycin respectively. When administered orally, the antibiotic peaks within 60 minutes. When given intramuscularly (IM), peak concentrations are reached between 1 to 3 hours. The half-life of clindamycin is approximately 3 hours in adults and approximately 2.5 hours in children, at which point it is excreted in the urine (major) and feces (minor) as active and inactive metabolites.

Administration

Clindamycin can be administered into the body by multiple routes. It is available topically as a foam, gel, lotion, or solution for treatment of acne vulgaris. A thin film needs to be applied twice a day. For the treatment of bacterial vaginosis, it is available in a cream and suppository to be administered intravaginally. Systemic infections can be treated orally with a capsule (75mg, 150mg, 300mg) or in solution (75mg/5mL). It is also available to be given as an intramuscular injection (9g/60mL, 300mg/2mL, 600mg/4mL, 900mg/6mL). Intravenous formulations are available as follows: clindamycin phosphate (300mg/2mL, 600mg/4mL, 900mg/6mL), and clindamycin phosphate in D5W or NaCl (300mg/50mL, 600mg/50mL, 900mg/50mL). To minimize esophageal ulceration, administer orally with a full glass of water. The absorption of clindamycin flavored granules is not adversely affected by co-administration with food. When administered intramuscularly, the sites must be rotated with no dose exceeding 600 mg in a single injection. Clindamycin is administered by intravenous (IV) intermittent infusion over at least 10 to 60 minutes at a maximum rate of 30 mg/minutes. The final concentration of the IV solution should not exceed 18 mg/mL. Pediatric dosing for neonates is 15 to 20 mg/kg per day given IM/IV divided over 6 to 8 hours. Infants, children, and adolescents are treated with 8 to 40 mg/kg per day orally divided over 3-4 doses. For IM/IV administration, 20 to 40mg/kg per day can be given over 3 to 4 doses.

Adverse Effects

The adverse effects of clindamycin vary based on how it is administered. The most common side effects experienced with topical use include pruritis, xeroderma, erythema, burning, exfoliation, or oily skin. With intravaginal administration, the most common side effects are vaginal candidiasis, pruritis, vulvovaginal disease, and vulvovaginitis. The primary adverse effects of clindamycin with systemic administration are pseudomembranous colitis, nausea, vomiting, and diarrhea. This is a result of clindamycin destroying much of the GI tract’s normal flora. Clostridium difficile is given the opportunity to overgrow in this environment. Toxins A and B, which are produced by C. difficile, causes Clostridium difficile-associated diarrhea (CDAD). Severe cases which result from hypertoxic-producing strains result in an increase in morbidity and mortality which may require colectomy for definitive treatment. Other adverse effects include thrombophlebitis or metallic taste with IV administration, azotemia, agranulocytosis, anaphylactic shock, abscess formation, induration, or irritation at the site of IM injection.

Contraindications

Clindamycin is contraindicated in patients with a history of pseudomembranous colitis or ulcerative colitis. Care needs to be taken in antibiotic use as bacterial and fungal superinfections may occur. It is also contraindicated in patients with hypersensitivity to clindamycin, lincomycin, or any of their components. Special care must also be taken in patients with atopic dermatitis as colonization is more prevalent in this patient population. Pathogenicity of skin infections is higher in this population. This is important for future infections as antibiotic resistance is a problematic complication.

Monitoring

Monitor for changes in bowel frequency, colitis and resolution of symptoms. Monitor liver function tests periodically in patients with severe liver disease. In prolonged therapy, monitor complete blood cell count (CBC), liver, and renal function. It is important to manage fluid and electrolyte replacement in this patient population adequately.

Toxicity

The most common adverse effects that occur with clindamycin toxicity are GI or allergic. There is no antidote for clindamycin toxicity, and the adverse effects will resolve with dose adjustment or discontinuation of the antibiotic. The treatment is supportive. It is recommended that serum electrolytes be measured in patients with vomiting and/or diarrhea. Vital signs need to be monitored along with CBC with differential, platelets, LFTs and renal function in patients who are symptomatic. It is also important to get an ECG and maintain continuous cardiac monitoring as cardiac arrhythmias, although rare, may occur. Evaluation for C. difficile toxin will be needed when colitis is suspected. It is important to look out for severe allergic reactions like DRESS or Steven-Johnson syndrome. In these situations, immediate discontinuation of the antibiotic is imperative along with supportive management that includes: IV fluids, oxygen therapy, diphenhydramine, and corticosteroids. In cases of severe hypotension, it may be necessary to administer fluid boluses and start vasopressors. Airway management is likely not necessary, but severe anaphylactic reactions will require airway management with endotracheal intubation. Rarely clindamycin toxicity will lead to cardiac arrhythmias and cardiac arrest in which case advanced cardiovascular life support will be required.